Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C14H23NO.C4H4O4 |
Molecular Weight | 337.4107 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.CC[C@H]([C@@H](C)CN(C)C)C1=CC=CC(O)=C1
InChI
InChIKey=JVHIGTLVLBJREO-HQOQZQJTSA-N
InChI=1S/C14H23NO.C4H4O4/c1-5-14(11(2)10-15(3)4)12-7-6-8-13(16)9-12;5-3(6)1-2-4(7)8/h6-9,11,14,16H,5,10H2,1-4H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t11-,14+;/m0./s1
Molecular Formula | C4H4O4 |
Molecular Weight | 116.0722 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
Molecular Formula | C14H23NO |
Molecular Weight | 221.3385 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/17656655Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21476608 | https://www.nucynta.com/hcp/er/mechanism-of-action#isi-0
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17656655
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21476608 | https://www.nucynta.com/hcp/er/mechanism-of-action#isi-0
Tapentadol is the first US FDA-approved centrally acting analgesic having both μ-opioid receptor agonist and noradrenaline (norepinephrine) reuptake inhibition activity with minimal serotonin reuptake inhibition. Tapentadol is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate, neuropathic pain associated with diabetic peripheral neuropathy (DPN) severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17656655 |
0.16 µM [Ki] | ||
Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17656655 |
8.8 µM [Ki] | ||
Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17656655 |
5.28 µM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | NUCYNTA Approved UseNUCYNTA ER (tapentadol) is indicated for the management of:
pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
neuropathic pain associated with diabetic peripheral neuropathy (DPN) severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Launch Date2008 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
221.34 ng/mL |
86 mg single, oral dose: 86 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAPENTADOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
221.34 ng × h/mL |
86 mg single, oral dose: 86 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAPENTADOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.16 h |
86 mg single, oral dose: 86 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAPENTADOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
4 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAPENTADOL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
80% |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
TAPENTADOL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
250 mg 2 times / day multiple, oral (max) Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: Page: p.424 |
unhealthy, 56.8 n = 894 Health Status: unhealthy Condition: Chronic low back pain|Osteoarthritis pain Age Group: 56.8 Sex: M+F Population Size: 894 Sources: Page: p.424 |
Disc. AE: Nausea, Constipation... AEs leading to discontinuation/dose reduction: Nausea (3.4%) Sources: Page: p.424Constipation (1.6%) Dizziness (3%) Vomiting (2.6%) Fatigue (1.8%) Somnolence (3.4%) Pruritus (0.6%) |
100 mg 6 times / day multiple, oral Recommended Dose: 100 mg, 6 times / day Route: oral Route: multiple Dose: 100 mg, 6 times / day Sources: Page: p.7 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.7 |
Disc. AE: Dizziness, Nausea... AEs leading to discontinuation/dose reduction: Dizziness Sources: Page: p.7Nausea Vomiting Somnolence Headache |
700 mg 6 times / day multiple, oral (total) Recommended Dose: 700 mg, 6 times / day Route: oral Route: multiple Dose: 700 mg, 6 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.1 |
Disc. AE: Respiratory depression, CNS disorder (NOS)... AEs leading to discontinuation/dose reduction: Respiratory depression Sources: Page: p.1CNS disorder (NOS) Intracranial pressure increased Abuse NOS Mental function decreased Physical impairment Seizures Serotonin syndrome (grade 4) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Pruritus | 0.6% Disc. AE |
250 mg 2 times / day multiple, oral (max) Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: Page: p.424 |
unhealthy, 56.8 n = 894 Health Status: unhealthy Condition: Chronic low back pain|Osteoarthritis pain Age Group: 56.8 Sex: M+F Population Size: 894 Sources: Page: p.424 |
Constipation | 1.6% Disc. AE |
250 mg 2 times / day multiple, oral (max) Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: Page: p.424 |
unhealthy, 56.8 n = 894 Health Status: unhealthy Condition: Chronic low back pain|Osteoarthritis pain Age Group: 56.8 Sex: M+F Population Size: 894 Sources: Page: p.424 |
Fatigue | 1.8% Disc. AE |
250 mg 2 times / day multiple, oral (max) Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: Page: p.424 |
unhealthy, 56.8 n = 894 Health Status: unhealthy Condition: Chronic low back pain|Osteoarthritis pain Age Group: 56.8 Sex: M+F Population Size: 894 Sources: Page: p.424 |
Vomiting | 2.6% Disc. AE |
250 mg 2 times / day multiple, oral (max) Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: Page: p.424 |
unhealthy, 56.8 n = 894 Health Status: unhealthy Condition: Chronic low back pain|Osteoarthritis pain Age Group: 56.8 Sex: M+F Population Size: 894 Sources: Page: p.424 |
Dizziness | 3% Disc. AE |
250 mg 2 times / day multiple, oral (max) Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: Page: p.424 |
unhealthy, 56.8 n = 894 Health Status: unhealthy Condition: Chronic low back pain|Osteoarthritis pain Age Group: 56.8 Sex: M+F Population Size: 894 Sources: Page: p.424 |
Nausea | 3.4% Disc. AE |
250 mg 2 times / day multiple, oral (max) Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: Page: p.424 |
unhealthy, 56.8 n = 894 Health Status: unhealthy Condition: Chronic low back pain|Osteoarthritis pain Age Group: 56.8 Sex: M+F Population Size: 894 Sources: Page: p.424 |
Somnolence | 3.4% Disc. AE |
250 mg 2 times / day multiple, oral (max) Recommended Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: Page: p.424 |
unhealthy, 56.8 n = 894 Health Status: unhealthy Condition: Chronic low back pain|Osteoarthritis pain Age Group: 56.8 Sex: M+F Population Size: 894 Sources: Page: p.424 |
Dizziness | Disc. AE | 100 mg 6 times / day multiple, oral Recommended Dose: 100 mg, 6 times / day Route: oral Route: multiple Dose: 100 mg, 6 times / day Sources: Page: p.7 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.7 |
Headache | Disc. AE | 100 mg 6 times / day multiple, oral Recommended Dose: 100 mg, 6 times / day Route: oral Route: multiple Dose: 100 mg, 6 times / day Sources: Page: p.7 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.7 |
Nausea | Disc. AE | 100 mg 6 times / day multiple, oral Recommended Dose: 100 mg, 6 times / day Route: oral Route: multiple Dose: 100 mg, 6 times / day Sources: Page: p.7 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.7 |
Somnolence | Disc. AE | 100 mg 6 times / day multiple, oral Recommended Dose: 100 mg, 6 times / day Route: oral Route: multiple Dose: 100 mg, 6 times / day Sources: Page: p.7 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.7 |
Vomiting | Disc. AE | 100 mg 6 times / day multiple, oral Recommended Dose: 100 mg, 6 times / day Route: oral Route: multiple Dose: 100 mg, 6 times / day Sources: Page: p.7 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.7 |
Abuse NOS | Disc. AE | 700 mg 6 times / day multiple, oral (total) Recommended Dose: 700 mg, 6 times / day Route: oral Route: multiple Dose: 700 mg, 6 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.1 |
CNS disorder (NOS) | Disc. AE | 700 mg 6 times / day multiple, oral (total) Recommended Dose: 700 mg, 6 times / day Route: oral Route: multiple Dose: 700 mg, 6 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.1 |
Intracranial pressure increased | Disc. AE | 700 mg 6 times / day multiple, oral (total) Recommended Dose: 700 mg, 6 times / day Route: oral Route: multiple Dose: 700 mg, 6 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.1 |
Mental function decreased | Disc. AE | 700 mg 6 times / day multiple, oral (total) Recommended Dose: 700 mg, 6 times / day Route: oral Route: multiple Dose: 700 mg, 6 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.1 |
Physical impairment | Disc. AE | 700 mg 6 times / day multiple, oral (total) Recommended Dose: 700 mg, 6 times / day Route: oral Route: multiple Dose: 700 mg, 6 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.1 |
Respiratory depression | Disc. AE | 700 mg 6 times / day multiple, oral (total) Recommended Dose: 700 mg, 6 times / day Route: oral Route: multiple Dose: 700 mg, 6 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.1 |
Seizures | Disc. AE | 700 mg 6 times / day multiple, oral (total) Recommended Dose: 700 mg, 6 times / day Route: oral Route: multiple Dose: 700 mg, 6 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.1 |
Serotonin syndrome | grade 4 Disc. AE |
700 mg 6 times / day multiple, oral (total) Recommended Dose: 700 mg, 6 times / day Route: oral Route: multiple Dose: 700 mg, 6 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Acute pain Sources: Page: p.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/200533Orig1s000PharmR.pdf#page=22 Page: 22.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Absorption, metabolism, and excretion of 14C-labeled tapentadol HCl in healthy male subjects. | 2007 Jul-Sep |
|
(-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. | 2007 Oct |
|
Single dose analgesic efficacy of tapentadol in postsurgical dental pain: the results of a randomized, double-blind, placebo-controlled study. | 2008 Dec |
|
Investigations into the drug-drug interaction potential of tapentadol in human liver microsomes and fresh human hepatocytes. | 2008 Jan |
|
The efficacy and tolerability of multiple-dose tapentadol immediate release for the relief of acute pain following orthopedic (bunionectomy) surgery . | 2008 Nov |
|
Tapentadol a 'realistic alternative' to strong opioids for severe pain. | 2008 Sep |
|
Tapentadol (Nucynta)--a new analgesic. | 2009 Aug 10 |
|
Tapentadol hydrochloride: a centrally acting oral analgesic. | 2009 Dec |
|
Efficacy and tolerability of tapentadol immediate release and oxycodone HCl immediate release in patients awaiting primary joint replacement surgery for end-stage joint disease: a 10-day, phase III, randomized, double-blind, active- and placebo-controlled study. | 2009 Feb |
|
Tapentadol approved as pain reliever. | 2009 Jan 1 |
|
Tapentadol hydrochloride: a next-generation, centrally acting analgesic with two mechanisms of action in a single molecule. | 2009 Jul |
|
A randomized, double-blind, placebo-controlled phase 3 study of the relative efficacy and tolerability of tapentadol IR and oxycodone IR for acute pain. | 2009 Jun |
|
A randomized, double-blind, phase III study comparing multiple doses of tapentadol IR, oxycodone IR, and placebo for postoperative (bunionectomy) pain. | 2009 Mar |
|
Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: a randomized, double-blind study. | 2009 May |
|
Schedules of controlled substances: placement of tapentadol into schedule II. Final rule. | 2009 May 21 |
|
Is tapentadol an advance on tramadol? | 2009 Nov |
|
Tapentadol immediate release for the relief of moderate-to-severe acute pain. | 2009 Nov |
|
The importance of the descending monoamine system for the pain experience and its treatment. | 2009 Oct 29 |
|
Efficacy and safety of Tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: a randomized, double-blind, placebo- and active-controlled phase III study. | 2010 |
|
Tapentadol for acute and chronic pain. | 2010 Aug |
|
Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study. | 2010 Aug |
|
[Tapentadol. Opioid analgesic and norepinephrine reuptake inhibitors]. | 2010 Dec |
|
Oral hydromorphone extended-release. | 2010 Dec |
|
Advances in perioperative pain management: use of medications with dual analgesic mechanisms, tramadol & tapentadol. | 2010 Dec |
|
Tapentadol, but not morphine, selectively inhibits disease-related thermal hyperalgesia in a mouse model of diabetic neuropathic pain. | 2010 Feb 12 |
|
Stereochemical basis for a unified structure activity theory of aromatic and heterocyclic rings in selected opioids and opioid peptides. | 2010 Feb 18 |
|
Tapentadol immediate release: a new treatment option for acute pain management. | 2010 Feb 8 |
|
Effects of acetaminophen, naproxen, and acetylsalicylic acid on tapentadol pharmacokinetics: results of two randomized, open-label, crossover, drug-drug interaction studies. | 2010 Jan |
|
In vitro and in vivo characterization of tapentadol metabolites. | 2010 Jan-Feb |
|
Dose conversion between tapentadol immediate and extended release for low back pain. | 2010 Jan-Feb |
|
Review of the effect of opioid-related side effects on the undertreatment of moderate to severe chronic non-cancer pain: tapentadol, a step toward a solution? | 2010 Jul |
|
Efficacy and safety of tapentadol prolonged release for chronic osteoarthritis pain and low back pain. | 2010 Jun |
|
Tapentadol immediate-release for acute pain. | 2010 Jun |
|
Neuropathy, retinopathy, and glucose-lowering treatments. | 2010 Jun |
|
Recent advances in postoperative pain management. | 2010 Mar |
|
Tapentadol: an initial analysis. | 2010 May-Jun |
|
Evaluation of study discontinuations with tapentadol inmmediate release and oxycodone immediate release in patients with low back or osteoarthritis pain. | 2010 May-Jun |
|
Determination of tapentadol and its metabolite N-desmethyltapentadol in urine and oral fluid using liquid chromatography with tandem mass spectral detection. | 2010 Oct |
|
Determination of tapentadol (Nucynta®) and N-desmethyltapentadol in authentic urine specimens by ultra-performance liquid chromatography-tandem mass spectrometry. | 2010 Oct |
|
Analgesic update: tapentadol hydrochloride. | 2010 Oct |
|
A thorough QT/QTc study of multiple doses of tapentadol immediate release in healthy subjects. | 2010 Oct |
|
Population pharmacokinetics of tapentadol immediate release (IR) in healthy subjects and patients with moderate or severe pain. | 2010 Oct |
|
Cost-effectiveness analysis of tapentadol immediate release for the treatment of acute pain. | 2010 Sep |
|
Tapentadol and its two mechanisms of action: is there a new pharmacological class of centrally-acting analgesics on the horizon? | 2010 Sep |
|
Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain. | 2010 Sep |
|
Tapentadol immediate release: a review of its use in the treatment of moderate to severe acute pain. | 2010 Sep 10 |
|
Long-term safety and tolerability of tapentadol extended release for the management of chronic low back pain or osteoarthritis pain. | 2010 Sep-Oct |
|
Comparative pharmacokinetics and bioavailability of tapentadol following oral administration of immediate- and prolonged-release formulations. | 2013 Apr |
|
Tapentadol hydrochloride: A novel analgesic. | 2013 Jul |
Sample Use Guides
As with many centrally-acting analgesic medications, the dosing regimen of NUCYNTA® should be individualized according to the severity of pain being treated, the previous experience with similar drugs and the ability to monitor the patient.
Initiate NUCYNTA® with or without food at a dose of 50 mg, 75 mg, or 100 mg every 4 to 6 hours depending upon pain intensity. On the first day of dosing, the second dose may be administered as soon as one hour after the first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg, 75 mg, or 100 mg every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability. Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been studied and are, therefore, not recommended.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27317026
Upon exposure to tramadol and tapentadol concentrations up to 600μM, cell toxicity was assessed through evaluation of oxidative stress, mitochondrial and metabolic alterations, as well as cell viability and death mechanisms through necrosis or apoptosis, and related signalling. Tapentadol was observed to trigger much more prominent toxic effects than tramadol, ultimately leading to energy deficit and cell death.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 19:01:43 GMT 2023
by
admin
on
Sat Dec 16 19:01:43 GMT 2023
|
Record UNII |
EJ39ME52AQ
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
1443156-37-3
Created by
admin on Sat Dec 16 19:01:43 GMT 2023 , Edited by admin on Sat Dec 16 19:01:43 GMT 2023
|
PRIMARY | |||
|
EJ39ME52AQ
Created by
admin on Sat Dec 16 19:01:43 GMT 2023 , Edited by admin on Sat Dec 16 19:01:43 GMT 2023
|
PRIMARY | |||
|
51042275
Created by
admin on Sat Dec 16 19:01:43 GMT 2023 , Edited by admin on Sat Dec 16 19:01:43 GMT 2023
|
PRIMARY | |||
|
1356394-87-0
Created by
admin on Sat Dec 16 19:01:43 GMT 2023 , Edited by admin on Sat Dec 16 19:01:43 GMT 2023
|
NON-SPECIFIC STOICHIOMETRY | |||
|
300000015560
Created by
admin on Sat Dec 16 19:01:43 GMT 2023 , Edited by admin on Sat Dec 16 19:01:43 GMT 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
SOLVATE->ANHYDROUS | |||
|
PARENT -> SALT/SOLVATE |
|
||
|
PARENT -> SALT/SOLVATE |
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |
|